This document describes our SPORE application entitled "Novel Targets for Prevention and Therapy of Breast Cancer". This program is based on the premise that molecules involved in the mitogenic, invasive and metastatic behavior of breast cancer as well as escape from hormone independence are identifiable and thus can be exploited for improved prognostication, therapy selection, and design of specific biologic therapies for treatment and prevention of disease. In this application a series of interactive research projects are focused on expanding our understanding of the pathogenetic significance of these molecules in breast cancer progression and exploiting this information to develop effective new strategies for breast cancer prevention and treatment. Specific targets chosen for translational research studies include heparin binding growth factors required for tumor induced angiogenesis (and thus critical in conversion from in situ to invasive breast cancer); a novel metalloproteinase secreted by breast cancer cells; newly discovered ligands of erbB2 which may play a role in breast cancer progression and therapy resistance, and the estrogen receptor. Preclinical and clinical studies of prognostic factors and therapies involving these breast cancer products are developed. A series of four novel cores is described including a tumor bank of fresh and frozen breast tumor materials, a repository of breast cancer cell lines, clinical breast cancer research resources and a unique mechanism of research coordination which support these projects and foster interaction with other institutional strengths and other SPOREs. A program for continued development of faculty committed to breast cancer research is described with specific examples of young faculty and their work which will benefit from this program. A portfolio of high priority pilot projects together with a system for prioritization and oversight is discussed which contribute directly to major SPORE projects and translational research activities. Finally, a coherent, tightly structured organization for the SPORE is described which provides accountability, flexibility and optimal interaction within the SPORE, within the institutional structure, and with other SPOREs to achieve the goal of improved outlook for women at risk of breast cancer and for patients already suffering from the disease.